Method of repairing age and disease immune dysfunction and cellular senescence with lymphoid stem cells and then re-applying those for therapeutic use

ABSTRACT

This invention relates to methods for treatment of diseases of aging including immunosenescence, immune dysfunction, inflammation and impairment of early lymphoid lineage differentiation. The invention more specifically relates to the use of granulocyte colony stimulating factors to assist in stem cell mobilization, optionally in combination with the application of a method of delivering precise magnetic field patterns which agree with the body&#39;s own natural magnetic field patterns, and further in combination with re-infusion of previously collected autologous cells and/or plasma, optionally including allogeneic (healthy donor) cells and blood plasma.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 16/534,720 filed Aug. 7, 2019, now pending; which is a continuationapplication of U.S. application Ser. No. 14/889,756 filed Nov. 6, 2015,now abandoned; which is a 35 USC § 371 National Stage application ofInternational Application No. PCT/US2014/037496 filed May 9, 2014, nowexpired; which claims the benefit under 35 USC § 119(e) to U.S.Application Ser. No. 61/893,444 filed Oct. 21, 2013 and to U.S.Application Ser. No. 61/821,319 filed May 9, 2013, both now expired. Thedisclosure of each of the prior applications is considered part of andis incorporated by reference in the disclosure of this application.

BACKGROUND OF THE INVENTION Field of the Invention

This invention relates to methods for treatment of diseases of agingincluding immunosenescence, immune dysfunction, inflammation andimpairment of early lymphoid lineage differentiation. The invention morespecifically relates to the use of granulocyte colony stimulatingfactors to assist in stem cell mobilization, optionally in combinationwith the application of a method of delivering precise magnetic fieldpatterns which agree with the body's own natural magnetic fieldpatterns, and further in combination with re-infusion of stem cellcontaining compositions, such as previously collected autologous cellsand/or plasma, optionally including allogeneic (healthy donor) cells andblood plasma.

Background Information

The phenomenon which manifests as growth arrest after a period ofapparently normal cell proliferation is known as Replicative Senescence(RS). Replicative Senescence is seen in a) cells from adults of all agesb) embryonic tissues, and c) animals.

Aging is associated with alterations of the immune system includingimpairments in innate immunity, T-lymphopoiesis and B-lymphopoiesis andthese impairments contribute to immunosenescence and immune dysfunctionin affected individuals. Multipotent hematopoietic stem cells (HSCs)aging contributes to impairments in early lymphoid lineagedifferentiation Immunosenescence with immune dysfunction and increasedinflammation is a primary cause of aging and diseases such as anemia,chronic diseases, autoimmune disorders, cancer, cardiovascular diseases,infection, metabolic diseases, neurodegenerative diseases, proteinenergy malnutrition and frailty.

Oscillating magnetic fields have been used for years in the course ofadministering physical therapy to clinic patients suffering from bonefractures. These devices are typically called bone growth stimulators.Bone growth occurs as a result of stem cell stimulation, activation anddifferentiation. These device signals, however, are a series of pulsesor oscillating waves, which have symmetry typical ofelectronic-generated signals (see FIG. 1 “Common electronic-generatedsignals”). More recently, researchers have discovered that the bodyemits its own complex electromagnetic field pattern. Unique patterns areassociated with immunosenescence and immune dysfunction, stress, ordisease. By capturing these abnormal patterns, re-storing andre-admitting these patterns to the target patient, researchers theorizethat the normal “healing process” may be restored more effectively, asthe patterns would be natural biologic patterns.

What is unique about the instantly disclosed method described is theconfluence of these unique processes to promulgate a therapeuticmodality.

The number of Cumulative population doublings (CPDs) cells undergo inculture varies considerably between cell types and species. Earlyresults suggested a relation between CPDs cells could endure and thelongevity of the species from which the cells were derived, e.g., cellsfrom the Galapagos tortoise, which can live over a century, divide about110 times while mouse cells divide roughly 15 times. Cells taken frompatients with progeroid syndromes such as Werner syndrome (WS)—exhibitfar fewer CPDs than normal humans. Certain “immortal” cell lines candivide indefinitely without reaching RS, e.g., embryonic germ cells andmost cell lines derived from tumors, such as HeLa cells.

Biomarkers of cell senescence include:

-   -   1) Growth arrest—Senescent cells are growth arrested in the        transition from phase G1 to phase S of the cell cycle. The        growth arrest in RS is irreversible in the sense that growth        factors cannot stimulate the cells to divide even though        senescent cells can remain metabolically active for long periods        of time;    -   2) Cellular morphology—Senescent cells are bigger and a        senescent population has more diverse morphotypes than cells at        earlier CPDs (Note FIG. 12 which shows Normal human fibroblasts        (left) and fibroblasts showing a senescent morphology (three        cells on the right). Notice the common elongated morphology of        senescent cells.    -   3) Senescence-associated β-galactosidase (SA β-gal) activity—In        vitro and in vivo, the percentage of cells positive for SA β-gal        increases with, respectively, CPDs and age. In immortal cell        lines, such as HeLa tumor cells, the percentage of cells        positive for SA β-gal does not correlate with CPDs. The increase        in SA β-gal also correlates with the appearance of the senescent        morphotypes;    -   4) Polyploid Increase—the percentage of polyploid cells—i.e.,        cells with three or more copies of chromosomes—has been shown to        increase. Deletions in the mitochondrial DNA (mtDNA) have also        been observed both during RS and during aging in vivo, at least        in some cells;    -   5) Change in Gene Expression Levels—The expression levels of        several genes change during in vitro cellular aging One        important type of gene overexpressed in senescent cells are        inflammatory regulators like interleukin 6 (IL6);        proinflammatory proteins secreted by senescent cells in driving        senescence, which may lead to positive feedback loops and to        senescence induction in normal cells near senescent cells;    -   6) Metalloproteinase and Heat Shock Protein Production—Senescent        cells also display an increased activity of metalloproteinases        which degrade the extracellular matrix and a decreased ability        to express heat shock proteins;    -   7) Telomere shortening—the primary cause of RS in human        fibroblasts which have a major role in aging.

SUMMARY OF THE INVENTION

The phenomenon which manifests as growth arrest after a period ofapparently normal cell proliferation is known as Replicative Senescence(RS). Replicative Senescence is seen in a) cells from adults of all agesb) embryonic tissues, and c) animals. The instant invention disclosestreatment modalities for treating a number of maladies which result fromthe aging process.

Aging is associated with alterations of the immune system includingimpairments in innate immunity, T-lymphopoiesis and B-lymphopoiesis andthese impairments contribute to immunosenescence and immune dysfunctionin affected individuals. Multipotent hematopoietic stem cells (HSCs)aging contributes to impairments in early lymphoid lineagedifferentiation Immunosenescence with immune dysfunction and increasedinflammation is a primary cause of aging and diseases such as anemia,chronic diseases, autoimmune disorders, cancer, cardiovascular diseases,infection, metabolic diseases, neurodegenerative diseases, proteinenergy malnutrition and frailty.

Oscillating magnetic fields have been used for years in the course ofadministering physical therapy to clinic patients suffering from bonefractures. These devices are typically called bone growth stimulators.Bone growth occurs as a result of stem cell stimulation, activation anddifferentiation. These device signals, however, are a series of pulsesor oscillating waves, which have symmetry typical ofelectronic-generated signals (see FIG. 1 “Common electronic-generatedsignals”). More recently, researchers have discovered that the bodyemits its own complex electromagnetic field pattern. Unique patterns areassociated with immunosenescence and immune dysfunction, stress, ordisease. By capturing these abnormal patterns, re-storing andre-admitting these patterns to the target patient, researchers theorizethat the normal “healing process” may be restored more effectively, asthe patterns would be natural biologic patterns. U.S. Pat. No. 7,361,136to Parker describes a method of treatment utilizing such a device and isincorporated by reference herein in its entirety.

The instantly disclosed method describes a therapeutic modality thatrepresents a confluence of one or more of these treatments.

Accordingly, it is a primary objective of the instant invention to treatdiseases of aging, diseases of aging with immunosenescence and immunedysfunction and inflammation, and impairments in early lymphoid lineagedifferentiation by use of a stem cell mobilization agents, G-CSF,Granulocyte Colony Stimulating Factor) in combination with one or moreof:

-   -   collecting autologous stem cells and plasma using a cell        collection device;    -   re-infusing the previously collected autologous cells and or        blood plasma;    -   re-infusing the previously collected autologous cells together        with allogeneic (healthy donor) cells and or blood plasma; and    -   re-infusing allogeneic (healthy donor) cells and or blood        plasma.

Treating diseases of aging and diseases of aging with immunosenescenceand immune dysfunction and inflammation by stem cell activation using amethod of delivering precise magnetic field patterns which agree withthe body's own natural magnetic field patterns, and do so with aninstrument capable of routine clinical therapy use, in combination withstem cell mobilization agents, G-CSF, Granulocyte Colony StimulatingFactor) in combination with one or more of:

-   -   collecting autologous cells and or plasma using a collection        device and re-infusing the previously collected autologous cells        and or blood plasma; and    -   re-infusing the previously collected autologous cells and or        blood plasma together with allogeneic (healthy donor) cells and        blood plasma.

Treating diseases of aging and diseases of aging with immunosenescenceand immune dysfunction and inflammation by stem cell activation using amethod of delivering precise magnetic field patterns which agree withthe body's own natural magnetic field patterns, utilizing an instrumentcapable of routine clinical therapy use, in combination with healthydonor allogeneic cells and/or blood plasma.

Treating diseases of aging and diseases of aging with immunosenescenceand immune dysfunction and inflammation by stem cell activation using amethod of delivering precise magnetic field patterns which agree withthe body's own natural magnetic field patterns, utilizing an instrumentcapable of routine clinical therapy use, in combination with stem cellmobilization agents, G-CSF, Granulocyte Colony Stimulating Factor).

Treating diseases of aging and diseases of aging with immunosenescenceand immune dysfunction and inflammation by stem cell activation using amethod of delivering precise magnetic field patterns which agree withthe body's own natural magnetic field patterns, utilizing an instrumentcapable of routine clinical therapy use.

Treating diseases of aging and diseases of aging with immunosenescenceand immune dysfunction and inflammation by stem cell activation using amethod of delivering precise magnetic field patterns which agree withthe body's own natural magnetic field patterns, utilizing an instrumentcapable of routine clinical therapy use, in combination with autologouscells and/or blood plasma.

Other objects and advantages of this invention will become apparent fromthe following description taken in conjunction with any accompanyingdrawings wherein are set forth, by way of illustration and example,certain embodiments of this invention. Any drawings contained hereinconstitute a part of this specification and include exemplaryembodiments of the present invention and illustrate various objects andfeatures thereof.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates common electronic-generated signals.

FIG. 2 illustrates the relationship between aging, immunosenescence,inflammation and disease states.

FIG. 3 illustrates a SQUID installation at Vanderbilt University.

FIG. 4 illustrates natural complex biologic waveforms found in the body.

FIG. 5 illustrates natural complex biologic waveforms of a frog nerve.

FIG. 6 illustrates the concept of extracting, analyzing and derivingwaveforms.

FIG. 7 illustrates magnetic field generation by current flow.

FIG. 8 illustrates use of a solenoid design field generator.

FIG. 9 illustrates a toroidal magnetic field applicator.

FIG. 10 illustrates a Helmholtz coil field applicator.

FIG. 11 illustrates a planar field applicator.

FIG. 12 illustration of normal versus senescent cell morphology.

FIG. 13 illustrates an effect of the inventive method on regulation oflevels of inflammatory and non-inflammatory markers in Patient 1.

FIG. 14 illustrates an effect of the inventive method on regulation oflevels of inflammatory and non-inflammatory markers in Patient 2.

FIG. 15 illustrates an effect of the inventive method on regulation oflevels of natural killer cells in Patient 2.

FIG. 16 illustrates an effect of the inventive method on regulation oflevels of inflammatory and non-inflammatory markers in Patient 3.

FIG. 17 illustrates an effect of the inventive method on regulation oflevels of naïve T cells in Patient 4.

FIG. 18 illustrates an effect of the inventive method on regulation oflevels of Central Memory T cells and Natural Killer cell activity inPatient 4.

FIG. 19 illustrates an effect of the inventive method on regulation oflevels of naïve T cells in Patient 5.

FIG. 20 illustrates an effect of the inventive method on regulation oflevels of Central Memory T cells in Patient 5.

FIG. 21 illustrates an effect of the inventive method on regulation oflevels of Natural Killer cell activity in Patient 5.

FIG. 22 illustrates an effect of the inventive method on regulation oflevels of Natural Killer cell activity in Patient 6.

FIG. 23 illustrates an effect of the inventive method on regulation oflevels of Natural Killer cell activity in Patient 7.

FIG. 24 is a SPECT Scan which demonstrates improvement in the patientsNeurodegenerative Disease following treatment in accordance with theinvention.

FIG. 25 illustrates an effect of the inventive method on regulation oflevels of Natural Killer cell activity in Patient 8.

FIG. 26 illustrates an effect of the inventive method on regulation oflevels of Total B cells in Patient 9.

FIG. 27 illustrates an effect of the inventive method on regulation oflevels of Memory T cells in Patient 9.

FIG. 28 illustrates an effect of the inventive method on regulation oflevels of naïve T cells in Patient 9.

FIG. 29 illustrates an effect of the inventive method on regulation oflevels of Natural Killer cell activity in Patient 9.

DETAILED DESCRIPTION OF THE INVENTION

Aging is associated with alterations of the immune system includingimpairments in innate immunity, T-lymphopoiesis and B-lymphopoiesis andthese impairments contribute to immunosenescence in affectedindividuals.

An altered differentiation capacity of Hematopoietic stem cells (HSCs)has been causally linked to a reduction in lymphopoiesis during aging inmice and in man. Whole genome expression analyses indicated that HSCintrinsic alterations in gene expression contribute to this phenotype.The pool of HSCs comprises different HSC subpopulations that are biasedtoward myeloid or lymphoid differentiation. There is evidence that uponaging myeloid-biased HSCs are maintained, whereas lymphoid-biased HSCsget lost. These result in the imbalance in myelolymphopoiesis occurringwith aging. The molecular causes of this age-associated selection of HSCsubpopulations remain to be delineated.

Accumulation of DNA damage has been associated with aging of IISCs inboth mice and man. Moreover, studies on telomerase knockout mice(Terc−/−) revealed evidence that chronic DNA damage signaling inresponse to telomere dysfunction leads to an acceleration ofhematopoietic skewing with a strong decrease in lymphopoiesis involvingboth cell intrinsic checkpoints and alterations in the blood circulatoryenvironment. HSC aging contributes to impairments in early lymphoidlineage differentiation. This process associates with a selectiveincrease of myeloid-competent HSCs and a decrease in lymphoid-competentIISCs during aging. This age-associated skewing in the maintenance ofsubpopulations of HSCs contributes to defects in lymphopoiesis anddecreasing immune function during aging. Molecular mechanisms that caninduce stem cell aging include the accumulation of DNA damage andtelomere dysfunction and it is possible that stem cell intrinsiccheckpoint as well as alteration in the stem cell environment (niche andsystemic environment) can contribute to age-dependent selection of HSCsubpopulations. The selective survival of distinct subpopulations ofHSCs also contributes to the development of malignancies in thehematopoietic system and the selective maintenance of myeloid-competentHSCs enhances the risk of mutation accumulation in the myeloid lineagethereby leading to an increase of myelo-proliferative diseases duringaging. The loss of lymphoid-competent HSCs may induce lymphoid lineagederived malignancies by impairing proliferative competition in lymphoidprogenitor cell niches. Along these lines it has been shown thatage-associated impairments in hematopoietic progenitor cellproliferation select for an outgrowth of malignant clones. In contrastto the possible influences on tumor promotion, it is conceivable thatthe depletion of HSC subpopulations could serve as a tumor suppressormechanism involved in the depletion of damaged HSCs. Cell surface markercombinations can subdivide human hematopoietic cells into differentsubpopulations which can also be subdivided into lymphoid-competentand/or myeloid-competent subpopulations during human aging. The stepwiseprocess of the lymphoid differentiation of multipotent hematopoieticstem cells (HSCs) in human bone marrow has been assumed to begin withexpression of the cell surface antigen CD10 (CALLA or MME) on CD34+progenitors, based on the finding that CD10+ progenitors lack myeloidand erythroid potential but are able to generate all lymphoid lineages.However, subsequent studies have shown that CD34+, CD10+ cells, eventhose without expression of lineage markers (Lin−: CD3−, CD14−, CD15−,CD19−, CD56−, CD235a−), show a strong bias toward B cell potential withrelatively little T cell or natural killer (NK) cell potential. CD34+,Lin−, CD10+ cells that lack expression of CD24 are precursors of theCD34+, Lin−CD1O+CD24+ population but nonetheless show molecular evidenceof commitment to the B cell lineage, with expression of several Bcell-specific genes. L-selectin (CD62L) is expressed on lymphocytes andmediates homing to peripheral lymphoid organs. Studies have reportedthat upregulation of CD62L expression on c-Kit+ Lin−Sca-1+ mouse bonemarrow cells correlate with loss of erythroid and megakaryocytepotential and efficient thymic engraftment. In the progenitor hierarchyof the lymphoid commitment of human cells, a stage of lymphoid primingthat precedes commitment to the B lymphoid lineage, either before orindependently of CD10 expression is a CD34+, Lin−, CD10− progenitorsubpopulation in human bone marrow that has high expression of CD62L andthat is devoid of clonogenic myeloid or erythroid potential. In stromalcultures, these cells are able to generate B cells, NK cells and Tcells, as well as monocytic and dendritic cells.

Aging is associated with alterations of the immune system includingimpairments in T-lymphopoiesis and B-lymphopoiesis and these impairmentscontribute to immunosenescence in affected individuals Immunosenescencewith immune dysfunction and increased inflammation is a primary cause ofaging and diseases such as anemia of chronic diseases, autoimmunedisorders, cancer, cardiovascular diseases, infection, metabolicdiseases, neurodegenerative diseases, and protein energy malnutrition.

Natural magnetic field waveforms have been discovered associated withbiologic processes ever since the discovery and development of the SQUID(FIG. 3 “SQUID installation at Vanderbilt University”). These waveformsappear in complex patterns such as shown here in (FIG. 4 “Naturalcomplex biologic waveforms found in the body”).

Although there is nothing new about the measurement and recording ofthese waveforms, the application of these waveforms in a useful clinicdevice has just recently been possible through the advance of modernelectronics. Thus, the method of identification, extraction andisolating and then delivering those magnetic field patterns in atherapeutically effective manner is a primary objective of the invention(FIG. 6 “Extract, analyze and derive”).

Researchers have theorized since the late 1960s that the informationcontent of a magnetic field waveform is received and recognized by thebody (if delivered in a specific manner) and is useful for therapeuticeffects. The modern bone growth stimulator is one example of such adevice, whereby this device has proven useful in medical applications toenhance the repair and growth of bone tissue. The method and device todeliver according to the method should, in theory, prove to be moreeffective in delivering medical therapy to a patient.

Natural biologic waveforms have been measured for many body processes.The graphic (FIG. 4 “Natural complex biologic waveforms found in thebody”) describes several of these processes. More recently,sophisticated and sensitive recording technology has been used to recordbiologic processes with even greater sensitivity, such as the firing ofa single nerve axon. Biologic waveforms have also been associated withspecific diseases and inflammatory processes which cause activation ofstem cells local to the disease site and being mobilized from the bonemarrow into the blood to reach the disease site. These waveforms arespeculated to have an association with the body's natural healingprocesses. Researchers have also speculated that externalelectromagnetic signals applied to the body are ignored unless they are:

-   -   Damaging signals, such as ionizing signals (e.g., X-Ray); or    -   Benign signals which affect a site of injury (e.g., diseases of        aging and diseases of aging with immunosenescence and immune        dysfunction and inflammation).

The device proposed herein is to deliver natural biologic waveformelectromagnetic fields to a site of injury, and so function moreeffectively than the signals used previously in combination with methodsof enhancing the concentration of stem cells at the disease sites. Themethod is the actual use of these natural biologic waveforms in thegeneration and delivery of those waveforms suited to a particularinjury.

Process to Capture, Store and Replicate Biologic Waveforms

The entire process begins with:

-   -   Discovery of the biologic signal    -   Isolation of the repair signal    -   Storage of the repair signal    -   Generation of the repair signal    -   Delivery of the repair signal    -   Conformity to a specified protocol

Discovery of the Biologic Signal

The discovery process begins with a known pathologic condition. Forexample, a cancer has well-understood biologic processes at work whichserve to repair the immune dysfunction and immune senescence andinflammation. These processes all involve the generation and emitting ofnatural biologic waveforms.

The discovery, therefore, begins with a patient who has a knowncondition and a sensitive measurement device, known as a SQUID(Superconductive QUantum Interference Device), to detect and measure thecondition waveforms. This device, or a representative of the device, isshown in FIG. 3 “SQUID installation at Vanderbilt University”. Thewaveforms generated by the body or biologic organisms have certainspecific characteristics. Examples of certain waveforms are shown inFIG. 5 “Natural complex biologic waveforms of a frog nerve”.

The measurement of the natural biologic waveform caused by theunderlying pathologic condition is facilitated by the SQUID apparatus,which is routinely used for measuring those types of waveforms.Conversely, the body may emit certain natural biologic waveforms thatare associated with the normal biologic function. That is, thosewaveforms are captured from a healthy subject.

Isolation of the Repair Signal

The natural biologic waveform of the patient target pathology and thepatient injury-free target are expected to differ in certaincharacteristics. In fact, Romanian researchers have reported in theliterature that these signals do indeed exist and can be isolated. Theisolation process may take place by digitizing those waveforms,analyzing and then performing certain digital operations on thepatterns, using pattern-recognition or other graphical technology.Isolation of the waveforms is a straightforward procedure, by whichmeasurements are taken of:

-   -   A healthy subject;    -   A subject with diseases of aging and diseases of aging with        immunosenescence and immune dysfunction and inflammation.

Each measurement is captured and digitized using mechanical orelectrical conversion means and placed into a common file format. Theprocedure to further isolate the suspected natural biologic signal is aprocess whereby a comparison of the two waveforms yields a “difference”waveform (see “Extract, analyze and derive” on page 10), which is thenpresented as the suspected biologic waveform contributing to the healingprocess.

The original source waveforms, e.g., the “Disease” waveform, and the“Normal” waveform are used as reference waveforms, in a study to comparethe relative effectiveness of those waveforms against the “difference”waveform.

Store of the Repair Signal

The final selected repair signal is then stored in electronic form,typically in a digitized fashion, or it may be stored in printedgraphical form. This may use a common flat-file or relational databasefor the electronic storage medium.

Generation of the Repair Signal

The stored electrical signal pattern is then re-generated in a device(here called a Modulator) which then powers an external applicator. There-generation of these electrical patterns may take place in a number ofways:

-   -   Using an internal digital look-up table    -   Using an internal derived equation, which is then solved    -   Using a series of signals, such as is found in a fourier series        Once the basic repair signal is then regenerated, it is then        modulated as to:    -   Frequency    -   Intensity    -   Duty Cycle by the generating device. This final signal is then        amplified and prepared for delivery to the patient or subject.

Delivery of the Repair Signal

The repair signal, having been captured, stored, processed andmodulated, is now ready to be delivered. Magnetic fields are deliveredby passing a current through a wire loop assembly of various forms, asis generically illustrated in FIG. 7. These types may be:

-   -   A solenoid    -   A toroid    -   A planar (or flat) coil    -   A Helmholtz coil

The solenoid magnetic field pattern may be seen in FIG. 8 “Use ofsolenoid design”. The toroid magnetic field patterns may be seen in FIG.9 “Toroidal magnetic field applicator”. The planar coil design may beseen on FIG. 11 “Planar field applicator”. The Helmholtz design may beseen on FIG. 10 “Helmholtz coil field applicator”.

Prior to delivering the current to the various types of applicators, theModulator power must amplify the stored signals to the level wherebythey may energize the coils. This amplification may require theexpenditure of power levels of up to 500 watts in the case of linearamplification, or may be significantly lower in the case of aswitching-type (digital) design.

Conformity to a Specified Protocol

The conformity to a specified protocol may require specifying certaintypes of stage treatment procedures. These procedures typically require:

-   -   A certain time of administered exposure    -   A certain time between exposures    -   A certain exposure dose    -   A certain dose design    -   A certain dose duty cycle

For example, the administered exposure may require stages exposures of30, 60 or 90 minute exposures over the course of several days. Theexposures may be staged according to a certain delay between eachexposure. The dosage may be adjusted up or down according to the needsof the subject. The dose design itself is specified, according to aselection of one or several types of waveforms which are stored in themachine, and the dose may have to regulated according to a certain dutycycle.

Various embodiments of the invention are illustrated in the followingexamples.

Example 1

This protocol will assess the efficacy of stem cell activation with stemcell mobilization using a granulocyte colony stimulating factor (g-csf)and autologous stem cell rich plasma to improve the levels of anti-agingbiomarkers in the recipients.

They will receive daily G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously for 5-7 days monthly for 12 months. Assessmentsmeasuring the anti-aging biomarkers and clinical markers of aging asreported via a 13-item Clinical evaluation will be done at baselinebefore starting treatments and will be repeated every 3 months duringthe treatment period, and every three months for 12 additional monthsafter the completion of the treatment period. Half of the recipientswill be randomly selected to also receive Autologous Stem Cell Richplasma in aliquots of 50 ml monthly for 12 months in the second 12-monthstudy period. The Autologous plasma donors are also plasma recipients.Autologous Donors will be dosed with G-CSF for three days prior toundergoing plasmapheresis. This will stimulate a significantly increasednumber of stem cells in the plasma.

The yield of stem cell rich plasma expected from the pheresis is about 2liters. The plasma will be divided into aliquots of about thirty-six 50ml doses and 5 ml testing aliquots. Samples will be frozen until suchtime as the same Plasma Recipient is being treated.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Safety Assessments

Baseline physical exam, blood chemistry will be done on all recipientsat baseline. These will be repeated after 3, 6, 9, and 12 months oftreatment, and quarterly for 1 year following the completion of the lasttreatment.

Safety and tolerability will be monitored through continuous reportingof adverse events.

Example 2

This protocol will assess the efficacy of stem cell activation with stemcell mobilization with granulocyte colony stimulating factor G-CSF) andautologous stem cell rich plasma to improve the levels of anti-agingbiomarkers in the recipients.

Patients will be treated with G-CSF stem cell mobilization andAutologous Stem Cell Rich Plasma to improve the levels of anti-agingbiomarkers in the recipients.

Primary Objective

During treatment, patients will continue to be evaluated for improvementin the levels of anti-aging biomarkers in the recipients duringtreatment for one year and for one year following the end of treatment.

Secondary Objectives

Improvement of clinical markers of aging as reported via a 13-itemClinical evaluation

Study Design

The study is classified as Phase I/II since it will be using along-standing safe ‘drug’ (G-CSF; Autologous plasma; ergo Phase II) butin a novel way (ergo Phase I).

They will receive daily G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously for 5-7 days monthly for 12 months. On the first ofthe 5-7 day period they will also receive Autologous Stem Cell Richplasma in aliquots of 50 ml monthly for 12 months. Assessments measuringthe biomarkers will be done at baseline before starting treatments andwill be repeated every 3 months during the treatment period, and everythree months for 12 additional months after the completion of thetreatment period. Additionally, clinical markers will be collected atthose same time points.

Autologous Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for 5-7 days for three days prior toundergoing plasma pheresis. This will stimulate a significantlyincreased number of stem cells in the plasma. The yield of stem cellrich plasma expected from the pheresis is about 2 liters. The plasmawill be divided into aliquots of about thirty-six 50 ml doses and 5 mltesting aliquots. Samples will be frozen until such time the same PlasmaRecipient is being treated.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1) Immunosenescence Panel    -   2) CCL 11    -   3) TGFBeta 1 growth factor    -   4) Nuclear Factor kappa beta (NFkB)    -   5) DHEA-S    -   6) Plasma Insulin    -   7) Telomere length    -   8) Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Example 3

This protocol will assess the efficacy of stem cell activation with stemcell mobilization with granulocyte colony stimulating factor (G-CSF) andautologous stem cell rich plasma in combination with infusing stem-cellrich plasma from ABO-matched cord blood healthy allogeneic donors toimprove the levels of anti-aging biomarkers in the recipients.

Patients will be treated with G-CSF stem cell mobilization andAutologous Stem Cell Rich Plasma in combination with Infusing Stem-CellRich Plasma from ABO-matched Healthy Cord Blood Allogeneic donors toimprove the levels of anti-aging biomarkers in the recipients.

Adults who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of G-CSF stem cellmobilization as well as Autologous Stem Cell Rich Plasma and Infusionsof Stem-Cell Rich Plasma from ABO-matched Healthy Cord Blood AllogeneicDonors will be treated monthly for a one-year period to determine ifthere is any improvement in those markers.

They will receive daily G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously for 5-7 days monthly for 12 months. On the first ofthe 5-7 day period they will also receive Autologous Stem Cell Richplasma in aliquots of 50 ml monthly for 12 months. After the end of thedaily G-CSF for the 5-7 day period they will also receive AllogeneicCord Blood Stem Cell Rich plasma in aliquots of 50 ml monthly for 12months. Assessments measuring the biomarkers will be done at baselinebefore starting treatments and will be repeated every 3 months duringthe treatment period, and every three months for 12 additional monthsafter the completion of the treatment period. Additionally, clinicalmarkers will be collected at those same time points.

Autologous Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for three days prior to undergoingplasmapheresis. This will stimulate a significantly increased number ofstem cells in the plasma.

The yield of stem cell rich plasma expected from the pheresis is about 2liters. The plasma will be divided into aliquots of about thirty-six 50ml doses and 5 ml testing aliquots. Samples will be frozen until suchtime as the same Plasma Recipient is being treated.

Allogeneic Cord Blood Plasma Donors

All donations of cord blood plasma will be taken from the plasmaextracted and normally discarded from healthy babies' cord bloodcollected from the delivered placenta at the time of birth and whosestem cells are to be cryopreserved for the baby's personal use at alater date.

The yield of plasma expected from the cord blood is about 55 mls. Theplasma will be divided into aliquots of 50 ml doses and 5 ml testingaliquots (for cross matching). Samples will be frozen until such time asa Plasma Recipient of the same AB 0/Rh type is being treated.

Based on the average prevalence of ABO types, it is anticipated that thenumber of donors needed will be approximately 12 to 15 per recipient.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Example 4

Recipients will be treated with G-CSF stem cell mobilization andAutologous Stem Cell Rich Plasma in combination with Infusing Stem-CellRich Plasma from ABO-matched Healthy Allogeneic Donors to improve thelevels of anti-aging biomarkers in the recipients.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of G-CSF stem cellmobilization as well as Autologous Stem Cell Rich Plasma and Infusionsof Stem-Cell Rich Plasma from ABO-matched Healthy Allogeneic Donors willbe treated monthly for a one-year period to determine if there is anyimprovement in those markers. I).

They will receive daily G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously for 5-7 days monthly for 12 months. On the first ofthe 5-7 day period they will also receive Autologous Stem Cell Richplasma in aliquots of 50 ml monthly for 12 months. After the end of thedaily G-CSF for the 5-7 day period they will also receive AllogeneicStem Cell Rich plasma in aliquots of 50 ml monthly for 12 months.Assessments measuring the biomarkers will be done at baseline beforestarting treatments and will be repeated every 3 months during thetreatment period, and every three months for 12 additional months afterthe completion of the treatment period. Additionally, clinical markerswill be collected at those same time points.

Autologous Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for three days prior to undergoingplasma pheresis. This will stimulate a significantly increased number ofstem cells in the plasma. The yield of stem cell rich plasma expectedfrom the pheresis is about 2 liters. The plasma will be divided intoaliquots of about thirty-six 50 ml doses and 5 ml testing aliquots.Samples will be frozen until such time the same Plasma Recipient isbeing treated.

Allogeneic Stem Cell Rich Plasma Donors

The other group making up the study population will be Allogeneic plasmadonors. Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for three days prior to undergoingplasma pheresis. This will stimulate a significantly increased number ofstem cells in the plasma. Donors will have Infectious Disease testingrepeated on the day of pheresis.

The yield of plasma expected from the pheresis is about 2 liters. Theplasma will be divided into aliquots of about thirty-six 50 ml doses and5 ml testing aliquots (for cross matching). Samples will be frozen untilsuch time as a Plasma Recipient of the same ABO/Rh type is beingtreated. Donors will be restricted to males and nulliparous females toavoid the presence of cytotoxic lymphocyte and granulocyte antibodies.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Example 5

This protocol will assess the efficacy of stem cell activation with stemcell mobilization with granulocyte colony stimulating factor (G-CSF) andin combination with infusing stem-cell rich plasma from AB 0-matchedhealthy allogeneic donors to improve the levels of anti-aging biomarkersin the recipients.

Patients will be treated with G-CSF stem cell mobilization and incombination with Infusing Stem-Cell Rich Plasma from ABO-matched HealthyAllogeneic Donors will be monitored for the improvement of levels ofanti-aging biomarkers in the recipients.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of G-CSF stem cellmobilization and Infusions of Stem-Cell Rich Plasma from ABO-matchedHealthy Allogeneic Donors will be treated monthly for a one-year periodto determine if there is any improvement in those markers. Recipientswill receive daily G-CSF at a dose of 5 to 15 ug/kg intravenously orsubcutaneously for 5-7 days monthly for 12 months. After the end of thedaily G-CSF for the 5-7 day period they will also receive AllogeneicStein Cell Rich plasma in aliquots of 50 ml monthly for 12 months.Assessments measuring the biomarkers will be done at baseline beforestarting treatments and will be repeated every 3 months during thetreatment period, and every three months for 12 additional months afterthe completion of the treatment period. Additionally, clinical markerswill be collected at those same time points.

Allogeneic Stem Cell Rich Plasma Donors Donors will be dosed with G-CSFat a dose of 5 to 15 ug/kg intravenously or subcutaneously for threedays prior to undergoing plasma pheresis. This will stimulate asignificantly increased number of stem cells in the plasma. The yield ofplasma expected from the pheresis is about 2 liters. The plasma will bedivided into aliquots of about thirty-six 50 ml doses and 5 ml testingaliquots (for cross matching). Samples will be frozen until such time asa Plasma Recipient of the same ABO/Rh type is being treated. Donors willbe restricted to males and nulliparous females to avoid the presence ofcytotoxic lymphocyte and granulocyte antibodies.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Example 6

This protocol will assess the efficacy of stem cell activation with stemcell mobilization with granulocyte colony stimulating factor (G-CSF) andautologous stem cell rich plasma in combination with infusing stem-cellrich plasma from ABO-matched healthy allogeneic donors to improve thelevels of anti-aging biomarkers in the recipients.

Patients will be treated with G-CSF stem cell mobilization andAutologous Stem Cell Rich Plasma in combination with Infusing Stem-CellRich Plasma from ABO-matched Healthy Allogeneic Donors in the hope ofimproving the levels of anti-aging biomarkers in the recipients.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of G-CSF stem cellmobilization as well as Autologous Stem Cell Rich Plasma and Infusionsof Stem-Cell Rich Plasma from ABO-matched Healthy Allogeneic Donors willbe treated monthly for a one-year period to determine if there is anyimprovement in those markers.

Recipients will receive daily G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for 5-7 days monthly for 12 months. Onthe first of the 5-7 day period they will also receive Autologous StemCell Rich plasma in aliquots of 50 ml monthly for 12 months. After theend of the daily G-CSF for the 5-7 day period they will also receiveAllogeneic Stem Cell Rich plasma in aliquots of 50 ml monthly for 12months. Assessments measuring the biomarkers will be done at baselinebefore starting treatments and will be repeated every 3 months duringthe treatment period, and every three months for 12 additional monthsafter the completion of the treatment period. Additionally, clinicalmarkers will be collected at those same time points.

Autologous Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for three days prior to undergoingplasma pheresis. This will stimulate a significantly increased number ofstem cells in the plasma. The yield of stem cell rich plasma expectedfrom the pheresis is about 2 liters. The plasma will be divided intoaliquots of about thirty-six 50 ml doses and 5 ml testing aliquots.Samples will be frozen until such time as the same Plasma Recipient isbeing treated.

Allogeneic Stem Cell Rich Plasma Donors

Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously for three days prior to undergoing plasma pheresis.This will stimulate a significantly increased number of stem cells inthe plasma. The yield of plasma expected from the pheresis is about 2liters. The plasma will be divided into aliquots of about thirty-six 50ml doses and 5 ml testing aliquots (for cross matching). Samples will befrozen until such time as a Plasma Recipient of the same ABO/Rh type isbeing treated. Donors will be restricted to males and nulliparousfemales to avoid the presence of cytotoxic lymphocyte and granulocyteantibodies.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCI, 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DIIEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Example 7

This protocol will assess the efficacy of stem cell activation with stemcell mobilization with granulocyte colony stimulating factor (G-C SF) incombination with infusing stem-cell rich plasma from ABO-matched cordblood allogeneic donors to improve the levels of anti-aging biomarkersin the recipients.

Patients will be treated with G-CSF stem cell mobilization incombination with Infusing Stem-Cell Rich Plasma from ABO-matched CordBlood Allogeneic Donors will improve the levels of anti-aging biomarkersin the recipients.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of G-CSF stem cellmobilization as well as Infusions of Stem-Cell Rich Plasma fromABO-matched Cord Blood Allogeneic Donors will be treated monthly for aone-year period to determine if there is any improvement in thosemarkers.

Recipients will receive daily G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for 5-7 days monthly. After the end ofthe daily G-CSF for the 5-7 day period, they will receive AllogeneicCord Blood Stem Cell Rich plasma in aliquots of 50 ml monthly for 12months. Assessments measuring the biomarkers will be done at baselinebefore starting treatments and will be repeated every 3 months duringthe treatment period, and every three months for 12 additional monthsafter the completion of the treatment period. Additionally, clinicalmarkers will be collected at those same time points.

Cord Blood Plasma Donors

All donations of cord blood plasma will be taken from the plasmaextracted and normally discarded from healthy babies' cord bloodcollected from the delivered placenta at the time of birth and whosestem cells are to be cryopreserved for the baby's personal use at alater date. The yield of plasma expected from the cord blood is about 55mls. The plasma will be divided into aliquots of about 50 ml doses and 5ml testing aliquots (for cross matching). Samples will be frozen untilsuch time as a Plasma Recipient of the same ABO/Rh type is beingtreated.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Example 8

This protocol will assess the efficacy of stem cell activation using therecipients own natural magnetic field patterns in combination with stemcell mobilization with granulocyte colony stimulating factor (G-CSF) andautologous stem cell rich plasma to improve the levels of anti-agingbiomarkers in the recipients.

Patients will be treated with G-CSF stem cell mobilization andAutologous Stem Cell Rich Plasma in Combination with administration ofprecise natural Magnetic fields to improve the levels of anti-agingbiomarkers in the recipients and improvement of clinical markers ofaging as reported via a 13-item Clinical evaluation

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of G-CSF stem cellmobilization as well as Autologous Stem Cell Rich Plasma andadministration of their own Precise Natural Magnetic fields will betreated monthly for a one-year period to determine if there is anyimprovement in those markers.

Recipients will receive daily G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for 5-7 days monthly for 12 months. Onthe first of the 5-7 day period they will also receive Autologous StemCell Rich plasma in aliquots of 50 ml and precise magnetic fieldpatterns which will agree with their body's own natural magnetic fieldpatterns monthly for 12 months. Assessments measuring the biomarkerswill be done at baseline before starting treatments and will be repeatedevery 3 months during the treatment period, and every three months for12 additional months after the completion of the treatment period.Additionally, clinical markers will be collected at those same timepoints.

Autologous Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for three days prior to undergoingplasma pheresis. This will stimulate a significantly increased number ofstem cells in the plasma. The yield of stem cell rich plasma expectedfrom the pheresis is about 2 liters. The plasma will be divided intoaliquots of about thirty-six 50 ml doses and 5 ml testing aliquots.Samples will be frozen until such time as the same Plasma Recipient isbeing treated.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Example 9

This protocol will assess the efficacy of stem cell activation using therecipients own natural magnetic field patterns in combination with stemcell mobilization with granulocyte colony stimulating factor (G-CSF) andautologous stem cell rich plasma in combination with infusing stem-cellrich plasma from ABO-matched healthy allogeneic donors to improve thelevels of anti-aging biomarkers in the recipients.

Patients will be treated with G-CSF stem cell mobilization andAutologous Stem Cell Rich Plasma in combination with Infusing Stem-CellRich Plasma from ABO-matched Healthy Allogeneic Donors in Combinationwith administration of Precise natural Magnetic fields to improve thelevels of anti-aging biomarkers in the recipients.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of G-CSF stem cellmobilization as well as Autologous Stem Cell Rich Plasma and Infusionsof Stein-Cell Rich Plasma from ABO-matched Healthy Allogeneic Donors andadministration of their own Precise Natural Magnetic fields monthly fora one-year period will be treated to determine if there is anyimprovement in those markers. The recipients will receive daily G-CSF ata dose of 5 to 15 ug/kg intravenously or subcutaneously for 5-7 daysmonthly for 12 months. On the first day of the 5-7 day period they willalso receive Autologous Stem Cell Rich plasma in aliquots of 50 ml andprecise magnetic field patterns which will agree with their body's ownnatural magnetic field patterns monthly for 12 months. After the end ofthe daily G-CSF for the 5-7 day period they will also receive AllogeneicStem Cell Rich plasma in aliquots of 50 ml monthly for 12 months.Assessments measuring the biomarkers will be done at baseline beforestarting treatments and will be repeated every 3 months during thetreatment period, and every three months for 12 additional months afterthe completion of the treatment period. Additionally, clinical markerswill be collected at those same time points.

Autologous Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for three days prior to undergoingplasmapheresis. This will stimulate a significantly increased number ofstem cells in the plasma. The yield of stem cell rich plasma expectedfrom the pheresis is about 2 liters. The plasma will be divided intoaliquots of about thirty-six 50 ml doses and 5 ml testing aliquots.Samples will be frozen until such time the same Plasma Recipient isbeing treated.

Allogeneic Stem Cell Rich Plasma Donors

Allogeneic plasma donors will be healthy, young adults (age 30 or less)with no major medical diagnoses. A physical exam and standard bloodchemistry and CBC will determine their eligibility. An ABO/Rh typing,hemoglobinopathy testing and antibody panel will be done on each donor,as well as Infectious Disease testing. Donors will be dosed with G-CSFat a dose of 5 to 15 ug/kg intravenously or subcutaneously for threedays prior to undergoing plasma pheresis. This will stimulate asignificantly increased number of stem cells in the plasma. Donors willhave Infectious Disease testing repeated on the day of pheresis. Theyield of plasma expected from the pheresis is about 2 liters. The plasmawill be divided into aliquots of about thirty-six 50 ml doses and 5 mltesting aliquots (for cross matching). Samples will be frozen until suchtime a Plasma Recipient of the same ABO/Rh type is being treated. Donorswill be restricted to males and nulliparous females to avoid thepresence of cytotoxic lymphocyte and granulocyte antibodies.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation. Baseline physical exam, blood chemistrywill be done on all recipients at baseline. These will be repeated after3, 6, 9, and 12 months of treatment, and quarterly for 1 year followingthe completion of treatment.

Example 10

This protocol will assess the efficacy of stem cell activation usingnatural magnetic field patterns in combination with infusing stem-cellrich plasma from ABO-matched healthy allogeneic donors to improve thelevels of anti-aging biomarkers in the recipients.

Recipients will be treated with plasma from healthy allogeneic donorswho have had stem cell mobilization in Combination with administrationof Precise natural Magnetic fields to improve the levels of anti-agingbiomarkers in the recipients of the plasma.

Adults who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of donor plasma and onthe same day they will also receive precise magnetic field patternswhich will agree with their body's own natural magnetic field patternswill be treated monthly for a one-year period to determine if there isany improvement in those markers. The recipients will receive ABO/Rhcross-matched plasma in aliquots of 50 ml monthly for 12 months. On thesame day they will receive administration of Precise natural Magneticfields. Assessments measuring the biomarkers will be done at baselineand every 3 months during the treatment period, and every three monthsfor 12 additional months after the completion of the treatment period.Additionally, clinical markers (group of 13) will be collected at thosesame time points.

Plasma Donors

All donors will be healthy, young adults (age 30 or less) with no majormedical diagnoses. A physical exam and standard blood chemistry and CBCwill determine their eligibility. An ABO/Rh typing and antibody panelwill be done on each donor, as well as Infectious Disease testing.Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously for three days prior to undergoing plasma pheresis.This will stimulate a significantly increased number of stem cells inthe plasma. Donors will have Infectious Disease testing repeated on theday of pheresis.

The yield of plasma expected from the pheresis is about 2 liters. Theplasma will be divided into aliquots of about thirty-six 50 ml doses and5 ml testing aliquots (for cross matching). Samples will be frozen untilsuch time as a Plasma Recipient of the same ABO/Rh type is beingtreated. Donors will be restricted to males and nulliparous females toavoid the presence of cytotoxic lymphocyte and granulocyte antibodies.

Recipients can be of any age or gender as long as they have nosignificant medical issues that would be contraindicated by the infusionof donor plasma and administration of precise magnetic field patternswhich will agree with their body's own natural magnetic field patterns.This will be determined by a physical exam and standard blood chemistryand CBC. Their ABO/Rh type will also be tested.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at baselineand at quarterly visits during physical exam that will provide secondaryefficacy data for evaluation. Baseline physical exam, blood chemistryand infectious disease markers will be done on all plasma donors andrecipients at baseline. These apart from infectious disease markers willbe repeated after 3, 6, 9, and 12 months of treatment, and quarterly for1 year following the completion of treatment.

Example 11

This protocol will assess the efficacy of stem cell activation usingnatural magnetic field patterns in combination with infusing stem-cellrich plasma from ABO-matched healthy cord blood allogeneic donors toimprove the levels of anti-aging biomarkers in the recipients.

Recipients will be treated with plasma from healthy Cord Bloodallogeneic donors in combination with administration of Precise naturalMagnetic fields to improve the levels of anti-aging biomarkers in therecipients of the plasma.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of Cord Blood donorplasma and on the same day they will also receive precise magnetic fieldpatterns which will agree with their body's own natural magnetic fieldpatterns will be treated monthly for a one-year period to determine ifthere is any improvement in those markers.

The recipients will receive ABO/Rh cross-matched Cord Blood plasma inaliquots of 50 ml monthly for 12 months. On the same day they willreceive administration of Precise natural Magnetic fields. Assessmentsmeasuring the biomarkers will be done at baseline and every 3 monthsduring the treatment period, and every three months for 12 additionalmonths after the completion of the treatment period. Additionally,clinical markers will be collected at those same time points.

All donations of cord blood plasma will be taken from the plasmaextracted and normally discarded from healthy babies' cord bloodcollected from the delivered placenta at the time of birth and whosestem cells are to be cryopreserved for the baby's personal use at alater date. The baby and mother will have no major medical diagnoses andthe mother will sign an informed consent form and agree to donation ofcord blood plasma. A physical exam and standard blood chemistry and CBCwill determine their eligibility. An ABO/Rh typing and antibody panelwill be done on each donor, as well as Infectious Disease testing.

The yield of plasma expected from the cord blood is about 55 mls. Theplasma will be divided into aliquots of 50 ml doses and 5 ml testingaliquots (for cross matching). Samples will be frozen until such time asa Plasma Recipient of the same ABO/Rh type is being treated. Based onthe average prevalence of ABO types, it is anticipated that the numberof donors needed will be approximately 12 to 15 per recipient.

Recipients can be of any age or gender as long as they have nosignificant medical issues that would be contraindicated by the infusionof donor plasma and administration of precise magnetic field patternswhich will agree with their body's own natural magnetic field patterns.This will be determined by a physical exam and standard blood chemistryand CBC. Their ABO/Rh type will also be tested.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at baselineand at quarterly visits during physical exam that will provide secondaryefficacy data for evaluation. Baseline physical exam, blood chemistryand infectious disease markers will be done on all plasma donors andrecipients at baseline. These apart from infectious disease markers willbe repeated after 3, 6, 9, and 12 months of treatment, and quarterly for1 year following the completion of treatment.

Example 12

This protocol will assess the efficacy of stem cell activation using therecipients own natural magnetic field patterns in combination with stemcell mobilization with granulocyte colony stimulating factor (G-CSF) toimprove the levels of anti-aging biomarkers in the recipients.

Patients will be treated with G-CSF stem cell mobilization incombination with administration of Precise natural Magnetic fields toimprove the levels of anti-aging biomarkers in the recipients.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of G-CSF stem cellmobilization and administration of their own Precise natural Magneticfields ill be treated monthly for a one-year period to determine ifthere is any improvement in those markers.

The recipients will receive daily G-CSF at a dose of 5 to 15 ug/kgintravenously or subcutaneously for 5-7 days monthly for 12 months. Onthe same day they will also receive precise magnetic field patternswhich will agree with their body's own natural magnetic field patterns.Assessments measuring the biomarkers will be done at baseline beforestarting treatments and will be repeated every 3 months during thetreatment period, and every three months for 12 additional months afterthe completion of the treatment period. Additionally, clinical markerswill be collected at those same time points. All recipients will have nomajor medical diagnoses which exclude them from undergoing G-CSF stemcell mobilization and administration of Precise natural Magnetic fieldswhich agree with the recipients own natural magnetic field patternsutilizing an instrument capable of routine clinical therapy use andassessment of response. A physical exam, standard blood chemistry, CBCand hemoglobinopathy testing will be done.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation. Baseline physical exam, blood chemistrywill be done on all recipients at baseline. These will be repeated after3, 6, 9, and 12 months of treatment, and quarterly for 1 year followingthe completion of treatment.

Example 13

This protocol will assess the efficacy of stem cell activation using therecipients own natural magnetic field patterns to improve the levels ofanti-aging biomarkers in the recipients.

Recipients will be treated by administration of Precise natural Magneticfields to improve the levels of anti-aging biomarkers.

Evaluation of the improvement in the levels of anti-aging biomarkers inthe recipients during treatment for one year and for one year followingthe end of treatments. Recipients who are interested in assessing theirlevel of anti-aging biomarkers, and who are willing to receive stem cellactivation using Precise natural Magnetic fields will be treated monthlyfor a one-year period to determine if there is any improvement in thosemarkers. Recipients will receive precise magnetic field patterns whichwill agree with their body's own natural magnetic field patterns monthlyfor 12 months. Assessments measuring the biomarkers will be done priorto the start of treatment and thereafter every 3 months during thetreatment period, and every three months for 12 additional months afterthe completion of the treatment period. Additionally, clinical markerswill be collected at those same time points. All recipients will have nomajor medical diagnoses which exclude them from receiving Precisenatural Magnetic fields which agree with the recipients own naturalmagnetic field patterns utilizing an instrument capable of routineclinical therapy use and assessment of response. A physical exam andstandard blood chemistry, CBC will determine their eligibility.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at baselineand at quarterly visits during physical exam that will provide efficacydata for evaluation. Baseline physical exam, blood chemistry andbiomarkers markers will be done on all recipients at baseline. Thesewill be repeated after 3, 6, 9, and 12 months of treatment, andquarterly for 1 year following the completion of treatment.

Example 14

This protocol will assess the efficacy of stem cell activation using therecipients own natural magnetic field patterns in combination withinfusing autologous stem-cell rich plasma to improve the levels ofanti-aging biomarkers in the recipients.

Recipients will be treated with autologous stem cell rich plasma fromrecipients who have had stem cell mobilization in combination withadministration of Precise natural Magnetic fields to improve the levelsof anti-aging biomarkers in the recipients. Evaluation of theimprovement in the levels of anti-aging biomarkers in the recipientsduring treatment for one year and for one year following the end oftreatment. Recipients who are interested in assessing their level ofanti-aging biomarkers, and who are willing to receive doses ofautologous stem cell rich donor plasma will be treated monthly for aone-year period to determine if there is any improvement in thosemarkers.

Recipients will receive Autologous Stem Cell Rich plasma in aliquots of50 ml monthly for 12 months. On the same day they will also receiveprecise magnetic field patterns which will agree with their body's ownnatural magnetic field patterns. Assessments measuring the biomarkerswill be done every 3 months during the treatment period, and every threemonths for 12 additional months after the completion of the treatmentperiod. Additionally, clinical markers will be collected at those sametime points.

All autologous donors who are also recipients will have no major medicaldiagnoses which exclude them from undergoing stem cell mobilization. Aphysical exam and standard blood chemistry, CBC, and Infectious Diseasemarker testing will determine their eligibility. Their ABO/Rh type willalso be tested.

Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously for three days prior to undergoing plasma pheresis.This will stimulate a significantly increased number of stem cells inthe plasma. Donors will have Infectious Disease testing repeated on theday of pheresis. ABO/Rh type will also be tested.

The yield of stem cell rich plasma expected from the pheresis is about 2liters. The plasma will be divided into aliquots of about thirty-six 50ml doses and 5 ml testing aliquots. Samples will be frozen until suchtime as the same Plasma Recipient is being treated.

Administration of Precise natural Magnetic fields which agree with therecipients own natural magnetic field patterns utilizing an instrumentcapable of routine clinical therapy use and response assessment.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation. Baseline physical exam, blood chemistryand infectious disease markers will be done on all plasma donors andrecipients at baseline. These apart from infectious disease markers willbe repeated after 3, 6, 9, and 12 months of treatment, and quarterly for1 year following the completion of treatment.

Example 15

This protocol will assess the efficacy of infusing stem-cell rich plasmafrom ABO-matched healthy donors to improve the levels of anti-agingbiomarkers in the recipients. Recipients will be treated with plasmafrom healthy donors who have had stem cell mobilization to improve thelevels of anti-aging biomarkers in the recipients of the plasma.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of donor plasma will betreated monthly for a one-year period to determine if there is anyimprovement in those markers.

The recipients will receive ABO/Rh cross-matched plasma in aliquots of50 ml monthly for 12 months. Assessments measuring the biomarkers willbe done every 3 months during the treatment period, and every threemonths for 12 additional months after the completion of the treatmentperiod. Additionally, clinical markers will be collected at those sametime points.

All donors will be healthy, young adults (age 30 or less) with no majormedical diagnoses. A physical exam and standard blood chemistry and CBCwill determine their eligibility. An ABO/Rh typing and antibody panelwill be done on each donor, as well as Infectious Disease testing.

Donors will be dosed with G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously for three days prior to undergoing plasma pheresis.This will stimulate a significantly increased number of stem cells inthe plasma. Donors will have Infectious Disease testing repeated on theday of pheresis.

The yield of plasma expected from the pheresis is about 2 liters. Theplasma will be divided into aliquots of about thirty-six 50 ml doses and5 ml testing aliquots (for cross matching). Samples will be frozen untilsuch time as a Plasma Recipient of the same ABO/Rh type is beingtreated. Donors will be restricted to males and nulliparous females toavoid the presence of cytotoxic lymphocyte and granulocyte antibodies.

Recipients can be of any age or gender as long as they have nosignificant medical issues that would be contraindicated by the infusionof donor plasma. This will be determined by a physical exam and standardblood chemistry and CBC. Their ABO/Rh type will also be tested.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation. Baseline physical exam, blood chemistryand infectious disease markers will be done on all plasma donors andrecipients at baseline. These apart from infectious disease markers willbe repeated after 3, 6, 9, and 12 months of treatment, and quarterly for1 year following the completion of treatment.

Example 16

This protocol will assess the efficacy of infusing stem-cell rich plasmafrom ABO-matched cord blood donors to improve the levels of anti-agingbiomarkers in the recipients.

Recipients will be treated with plasma from Cord Blood donors to improvethe levels of anti-aging biomarkers in the recipients of the plasma.Evaluation of the improvement in the levels of anti-aging biomarkers inthe recipients during treatment for one year and for one year followingthe end of treatment. Improvement of clinical markers of aging asreported via a 13-item Clinical evaluation.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive doses of donor plasma monthlyfor a one-year period will be treated to determine if there is anyimprovement in those markers.

The recipients will receive ABO/Rh cross-matched Cord Blood Plasma inaliquots of 50 ml monthly for 12 months. Assessments measuring thebiomarkers will be done every 3 months during the treatment period, andevery three months for 12 additional months after the completion of thetreatment period. Additionally, clinical markers will be collected atthose same time points.

All donations of cord blood plasma will be taken from the plasmaextracted and normally discarded from healthy babies' cord bloodcollected from the delivered placenta at the time of birth and whosestem cells are to be cryopreserved for the baby's personal use at alater date. The baby and mother will have no major medical diagnoses andthe mother will sign an informed consent form and agree to donateplasma. A physical exam and standard blood chemistry and CBC willdetermine their eligibility. An ABO/Rh typing and antibody panel will bedone on each donor, as well as Infectious Disease testing. The yield ofplasma expected from the cord blood is about 55 mls. The plasma will bedivided into aliquots of about 50 ml doses and 5 ml testing aliquots(for cross matching). Samples will be frozen until such time as a PlasmaRecipient of the same ABO/Rh type is being treated.

Recipients can be of any age or gender as long as they have nosignificant medical issues that would be contraindicated by the infusionof donor plasma. This will be determined by a physical exam and standardblood chemistry and CBC. Their ABO/Rh type will also be tested.

There will be eight primary biomarker measurements evaluated atbaseline, and after treatment for 3 months, 6 months, 9 months, and 12months. These same evaluations will continue every three months for anadditional year to examine the long-term effect of the treatment. Theseassessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

Example 18

This protocol will assess the efficacy of G-CSF (granulocyte colonystimulating factor) mobilization of CD34+ peripheral blood stem cells toimprove the levels of anti-aging biomarkers in the recipients.

Patients will be treated with stem cell mobilization factor to improvethe levels of anti-aging biomarkers in the recipients. Evaluation of theimprovement in the levels of anti-aging biomarkers in the recipientsduring treatment for one year and for one year following the end oftreatment. Improvement of clinical markers of aging as reported via a13-item Clinical evaluation.

Recipients who are interested in assessing their level of anti-agingbiomarkers, and who are willing to receive G-CSF Mobilization for aone-year period will be treated to determine if there is any improvementin those markers.

The recipients will receive initially 3 cycles of G-CSF mobilizationfollowed by 1 cycle at 3 months, 6 months, 9 months and 12 months. EachCycle consists of daily G-CSF at a dose of 5 to 15 ug/kg intravenouslyor subcutaneously per day administered subcutaneously for 3 to 7 daysfollowed by 7 days off G-CSF with evaluation on 3 of the 7 off days.Assessments measuring the biomarkers will be done every 3 months duringthe treatment period, and every three months for 12 additional monthsafter the completion of the treatment period. Additionally, clinicalmarkers will be collected at those same time points.

Recipients who sign an informed consent form can be of any age or genderas long as they have no significant medical issues that would becontraindicated by the subcutaneous administration of G-CSF. This willbe determined by a physical exam and standard blood chemistry and CBC.Their hemoglobinopathy screen will also be tested. There will be eightprimary biomarker measurements evaluated at baseline, and aftertreatment for 3 months, 6 months, 9 months, and 12 months. These sameevaluations will continue every three months for an additional year toexamine the long-term effect of the treatment. These assessments are:

-   -   1. Immunosenescence Panel    -   2. CCL 11    -   3. TGFBeta 1 growth factor    -   4. Nuclear Factor kappa beta (NFkB)    -   5. DHEA-S    -   6. Plasma Insulin    -   7. Telomere length    -   8. Cytokine Multiplex 18

There will also be clinical markers (group of 13) evaluated at thequarterly visits during physical exam that will provide secondaryefficacy data for evaluation.

In accordance with the protocol set forth in Example 18, severalpatients were treated. These patients, their conditions, and treatmentwill now be summarized with reference to FIGS. 13-29.

Regarding Patient 1, reference is made to FIG. 13.

Diagnosis: Anemia, Chronic Disease (Chronic Obstructive PulmonaryDisease), Cardiovascular Disease (Chronic Heart Failure), Protein energymalnutrition, and Frailty.

In accordance with the basic protocol outlined in Example 18, a patientMR was treated with stem cell mobilization factor, G-CSF to improve thelevels of anti-aging biomarkers in the patient. Evaluation of the levelsof anti-inflammatory (IL-10) and inflammatory (TNF-alpha) agingbiomarkers during treatment was carried out. An improvement in the levelof the clinical marker of aging, IL-10 was reported. After 3 months oftreatment, during which time the patient was administered G-CSF as inExample 18, levels of IL-10 improved from 4.54 to 9.489.

Evaluation of the improvement in the levels of inflammatory agingbiomarkers during treatment was carried out. A decrease in the level ofthe inflammatory clinical marker of aging, TNF-alpha was reported. After3 months of treatment, during which time the patient was administeredG-CSF as in Example 18, levels of TNF-alpha went from 20.636 to 9.997.

While not wishing to be bound to any particular theory of operation,reduction in TNF-alpha and increase in IL-10 resulted in improvement inclinical symptoms of inflammation and immunosenescence associated withAnemia, Chronic Disease (Chronic Obstructive Pulmonary Disease),Cardiovascular Disease (Chronic Heart Failure), Protein energymalnutrition, Frailty.

Regarding Patient 2, reference is made to FIGS. 14 and 15.

Diagnosis: Cancer, Protein energy malnutrition, Frailty.

In accordance with the basic protocol outlined in Example 18, a patientDP was treated with stem cell mobilization factor, G-CSF to improve thelevels of aging biomarkers in the patient. Evaluation of the levels ofanti-inflammatory (IL-10) and inflammatory (TNF-alpha) aging biomarkersduring treatment was carried out. An improvement in the level of theclinical marker of aging, IL-10 was reported. After 3 months oftreatment, during which time the patient was administered G-CSF as inExample 18, levels of IL-10 improved from 1.787 to 5.774.

Evaluation of the improvement in the levels of inflammatory agingbiomarkers during treatment was carried out. A decrease in the level ofthe inflammatory clinical marker of aging, TNF-alpha was reported. After3 months of treatment, during which time the patient was administeredG-CSF as in Example 18, levels of TNF-alpha decreased from 11.072 to7.243. After 3 months of treatment, during which time the patient wasadministered G-CSF as in Example 18, levels of Natural Killer Cellsincreased from 82 to 183.

While not wishing to be bound to any particular theory of operation,reduction in TNF-alpha and increase in IL-10 and Natural Killer Cellsresulted in improvement in clinical symptoms of inflammation andimmunosenescence associated with Cancer, Protein energy malnutrition,Frailty.

Regarding Patient 3, reference is made to FIG. 16.

Diagnosis: Chronic disease, Neurodegenerative Disease, Frailty.

In accordance with the basic protocol outlined in Example 18, a patientJB was treated with stem cell mobilization factor, G-CSF to improve thelevels of aging biomarkers in the patient. Evaluation of the levels ofanti-inflammatory (IL-10) and inflammatory (TNF-alpha) aging biomarkersduring treatment was carried out. An improvement in the level of theclinical marker of aging, IL-10 was reported. After 3 months oftreatment, during which time the patient was administered G-CSF as inExample 18, levels of IL-10 improved from 4.326 to 6.264.

Evaluation of the improvement in the levels of inflammatory agingbiomarkers during treatment was carried out. A decrease in the level ofthe inflammatory clinical marker of aging, TNF-alpha was reported. After3 months of treatment, during which time the patient was administeredG-CSF as in Example 18, levels of TNF-alpha decreased from 9.469 to3.832.

While not wishing to be bound to any particular theory of operation,reduction in TNF-alpha and increase in IL-10 resulted in improvement inclinical symptoms of inflammation and immunosenescence associated withChronic disease, Neurodegenerative Disease, Frailty.

Regarding Patient 4, reference is made to FIGS. 17 and 18.

Diagnosis: Chronic Metabolic Disease, Diabetes Mellitus Type 2, Frailty.

In accordance with the basic protocol outlined in Example 18, a patientRA was treated with stem cell mobilization factor, G-CSF to improve thelevels of aging biomarkers in the patient. Evaluation of the improvementin the levels of aging, immunosenescence, immune dysfunction, and earlylymphoid lineage differentiation biomarkers during treatment was carriedout. An improvement with an increase in the level of the Naïve CD4 andCD8 levels and a decrease in the Memory CD4 T cells and improvement inNatural Killer Cell Activity were reported. After 2 months of treatment,during which time the patient was administered G-CSF as in Example 18,levels of Naïve CD4 improved from 4.88 to 12.46. Levels of Naïve CD8improved from 14.62 to 24.17.

Evaluation of the improvement was observed with a decrease in the levelsof Memory CD4 T Cells from 80.37 to 68.52.

Also, an improvement in Natural Killer Cell Activity was reported after2 months of treatment, during which time the patient was administeredG-CSF as in Example 18, wherein levels of Natural Killer Cell ActivityCD4 improved from 9.46 to 18.36.

While not wishing to be bound to any particular theory of operation,reduction in Central Memory T cells and increase in Naïve T cells andNatural Killer Cell Activity resulted in improvement in clinicalsymptoms of immune dysfunction, immunosenescence and impairment of earlylymphoid differentiation associated with Chronic Metabolic Disease,Diabetes Mellitus Type 2, and Frailty.

Regarding Patient 5, reference is made to FIGS. 19-21.

Diagnosis: Chronic disease, Cancer (Waldenstroms Macroglobulinemia),Neurodegenerative Disease (Peripheral Neuropathy), Frailty.

In accordance with the basic protocol outlined in Example 18, a patientDS was treated with stem cell mobilization factor, G-CSF to improve thelevels of aging biomarkers in the patient. Evaluation of the improvementin the levels of aging, immunosenescence, immune dysfunction, and earlylymphoid lineage differentiation biomarkers during treatment was carriedout. An improvement with an increase in the level of the Naïve CD4levels and a decrease in the Memory CD4 T cells and improvement inNatural Killer Cell Activity was reported. After 2 months of treatment,during which time the patient was administered G-CSF as in Example 18,levels of Naïve CD4 improved from 12.08 to 42.47.

Evaluation of the improvement in immune dysfunction was further observedwith a decrease in the levels of Memory CD4 T Cells decreased from 78.09to 40.90.

Also, an improvement in Natural Killer Cell Activity was reported after2 months of treatment, during which time the patient was administeredG-CSF as in Example 18, levels of Natural Killer Cell Activity CD4improved from 1.93 to 7.22.

While not wishing to be bound to any particular theory of operation,reduction in Central Memory T cells and increase in Naïve T cells andNatural Killer Cell Activity resulted in improvement in clinicalsymptoms of immune dysfunction, immunosenescence and impairment of earlylymphoid differentiation associated with Chronic disease, Cancer(Waldenstroms Macroglobulinemia), Neurodegenerative Disease (PeripheralNeuropathy), and Frailty.

Regarding Patient 6, reference is made to FIG. 22.

Diagnosis: Chronic disease, Chronic Infection (Lyme's Disease),Neurodegenerative Disease.

In accordance with the basic protocol outlined in Example 18, a patientSH was treated with stem cell mobilization factor, G-CSF to improve thelevels of aging biomarkers in the patient. Evaluation of the improvementin the levels of aging, immunosenescence, and immune dysfunctionbiomarkers during treatment was carried out. An improvement with anincrease in the level of Natural Killer Cells was reported. After 2months of treatment, during which time the patient was administeredG-CSF as in Example 18, levels of Natural Killer Cells improved from 268to 623.

While not wishing to be bound to any particular theory of operationincrease in Natural Killer Cells resulted in improvement in clinicalsymptoms of immune dysfunction, and immunosenescence associated withChronic disease, Chronic Infection (Lyme's Disease), andNeurodegenerative Disease.

Regarding Patient 7, reference is made to FIGS. 23 and 24.

Diagnosis: Chronic disease, Chronic Fatigue Syndrome, NeurodegenerativeDisease, Autoimmune Disease (Type 1 Diabetes Mellitus).

In accordance with the basic protocol outlined in Example 18, a patientLS was treated with stem cell mobilization factor, G-CSF to improve thelevels of aging biomarkers in the patient. Evaluation of the improvementin the levels of aging, immunosenescence, and immune dysfunctionbiomarkers during treatment was carried out. An improvement with anincrease in the level of Natural Killer Cells was reported. After 2months of treatment, during which time the patient was administeredG-CSF as in Example 18, levels of Natural Killer Cells improved from 47to 120.

After the 2 months of treatment, during which time the patient wasadministered G-CSF as in Example 18 SPECT Scans (FIG. 24) showedimprovement in the patients Neurodegenerative Disease.

After the 2 months of treatment, during which time the patient wasadministered G-CSF as in Example 18 the patient's insulin requirementfor Type 1 Diabetes Mellitus decreased by 50%.

While not wishing to be bound to any particular theory of operation,increase in Natural Killer Cells and results of SPECT Scans wereindicative of improvement in clinical symptoms of immune dysfunction andimmunosenescence associated with Chronic disease, Chronic FatigueSyndrome, Neurodegenerative Disease and Type 1 Diabetes Mellitus.

Regarding Patient 8, reference is made to FIG. 25.

Diagnosis: Chronic disease, Chronic Viral Infection.

In accordance with the basic protocol outlined in Example 18, a patientBF was treated with stem cell mobilization factor, G-CSF to improve thelevels of aging biomarkers in the patient. Evaluation of the improvementin the levels of aging, immunosenescence, and immune dysfunctionbiomarkers during treatment was carried out. An improvement with anincrease in the level of Natural Killer Cells Activity was reported.After 2 months of treatment, during which time the patient wasadministered G-CSF as in Example 18, levels of Natural Killer CellsActivity improved from 3.02 to 35.44.

While not wishing to be bound to any particular theory of operation,increase in Natural Killer Cells resulted in improvement in clinicalsymptoms of immune dysfunction and immunosenescence associated withChronic disease and Chronic Viral Infection.

Regarding Patient 9, reference is made to FIGS. 26-29.

Diagnosis: Chronic disease, Cancer (Colon Cancer), Frailty.

In accordance with the basic protocol outlined in Example 5, a patientLK was treated with stem cell activation with stem cell mobilizationwith granulocyte colony stimulating factor (G-CSF) and in combinationwith infusing stem-cell rich plasma from ABO-matched healthy allogeneicdonors to improve the levels of anti-aging biomarkers in the recipients.

Evaluation of the improvement in the levels of aging, immunosenescence,immune dysfunction, and early lymphoid lineage differentiationbiomarkers during treatment was carried out. An improvement with anincrease in the level of the Naïve CD4 levels and a decrease in theMemory CD4 T cells and improvement in Natural Killer Cell Activity wasreported. After 12 months, during which time the patient wasadministered G-CSF as in Example 5, levels of Naïve CD4 cells improvedfrom 30.00 to 51.79.

Evaluation of the improvement in immune dysfunction resulted in adecrease in the levels of Memory CD4 T Cells from 60.24 to 38.53.

Also, an improvement in Natural Killer Cell Activity was reported after12 months, during which time the patient was treated as in Example 5,wherein levels of Natural Killer Cell Activity improved from 7.21 to19.26.

Also, an improvement in B Cell was reported after 12 months oftreatment, during which time the patient was treated as in Example 5,wherein levels of B Cells improved from 36 to 46.

While not wishing to be bound to any particular theory of operation,reduction in Central Memory T cells and increase in Naïve T cells, BCells and Natural Killer Cell Activity resulted in improvement inclinical symptoms of immune dysfunction, immunosenescence and impairmentof early lymphoid differentiation associated with Chronic disease,Cancer (Colon Cancer), Frailty.

All patents and publications mentioned in this specification areindicative of the levels of those skilled in the art to which theinvention pertains. All patents and publications are herein incorporatedby reference to the same extent as if each individual publication wasspecifically and individually indicated to be incorporated by reference.

It is to be understood that while a certain form of the invention isillustrated, it is not to be limited to the specific form or arrangementherein described and shown. It will be apparent to those skilled in theart that various changes may be made without departing from the scope ofthe invention and the invention is not to be considered limited to whatis shown and described in the specification and any drawings/figuresincluded herein.

One skilled in the art will readily appreciate that the presentinvention is well adapted to carry out the objectives and obtain theends and advantages mentioned, as well as those inherent therein. Theembodiments, methods, procedures and techniques described herein arepresently representative of the preferred embodiments, are intended tobe exemplary and are not intended as limitations on the scope. Changestherein and other uses will occur to those skilled in the art which areencompassed within the spirit of the invention and are defined by thescope of the appended claims. Although the invention has been describedin connection with specific preferred embodiments, it should beunderstood that the invention as claimed should not be unduly limited tosuch specific embodiments. Indeed, various modifications of thedescribed modes for carrying out the invention which are obvious tothose skilled in the art are intended to be within the scope of thefollowing claims.

What is claimed is:
 1. A method of treating an aging subject comprising:a) preparing an allogeneic stem cell rich plasma composition byadministering to a young healthy donor a stem cell mobilization agent inan amount and for a time period sufficient to stimulate a significantlyincreased number of stem cells in the blood of the donor; b) obtaining asufficient volume of plasma by plasmapheresis from the donor blood byseparating cellular material from the blood and retaining the stem cellrich plasma; and c) administering the allogeneic stem cell rich plasmacomposition to the aging recipient who has the ABO/Rh blood type of saiddonor, wherein upon administration of the plasma to the aging recipientin need thereof, the plasma induces a change in at least one or acombination of biomarkers, thereby treating the aging subject.
 2. Atherapeutic composition comprising an allogeneic stem cell rich plasmaformulated for intravenous administration to a subject.
 3. The method ofclaim 1, wherein the plasma is formulated for intravenousadministration.
 4. A method of treating an aging subject comprising: a)obtaining a sufficient volume of plasma by plasmapheresis from donorblood by separating cellular material from the blood and retainingallogeneic stem cell rich plasma, wherein the allogeneic stem cell richplasma composition is first prepared by administering to a young healthydonor a stem cell mobilization agent in an amount and for a time periodsufficient to stimulate a significantly increased number of stem cellsin the blood of the donor; and b) administering the allogeneic stem cellrich plasma composition to the aging recipient who has the ABO/Rh bloodtype of said donor, wherein upon administration of the plasma to theaging recipient in need thereof, the plasma induces a change in at leastone or a combination of biomarkers, thereby treating the aging subject.5. A method of treating a subject suffering from an alteration of theimmune system comprising: a) preparing an allogeneic stem cell richplasma composition by administering to a young healthy donor a stem cellmobilization agent in an amount and for a time period sufficient tostimulate a significantly increased number of stem cells in the blood ofthe donor; b) obtaining a sufficient volume of plasma by plasmapheresisfrom the donor blood by separating cellular material from the blood andretaining the stem cell rich plasma; and c) administering the allogeneicstem cell rich plasma composition to the subject suffering from analteration of the immune system and having the ABO/Rh blood type of saiddonor, wherein upon administration of the plasma to the subject, theplasma induces a change in at least one or a combination of biomarkers,thereby treating the subject.
 6. The method of claim 5, wherein thealteration of the immune system is immunosenescence, immune dysfunction,or inflammation.
 7. The method of claim 5, wherein the alteration of theimmune system is associated with aging.
 8. The method of claim 5,wherein the subject suffers from cancer.
 9. The method of claim 5,wherein said stem cell mobilization agent is a granulocyte colonystimulating factor (G-CSF).
 10. A method of treating a subject sufferingfrom an immune disorder comprising: a) preparing an allogeneic stem cellrich plasma composition by administering to a young healthy donor a stemcell mobilization agent in an amount and for a time period sufficient tostimulate a significantly increased number of stem cells in the blood ofthe donor; b) obtaining a sufficient volume of plasma by plasmapheresisfrom the donor blood by separating cellular material from the blood andretaining the stem cell rich plasma; and c) administering the allogeneicstem cell rich plasma composition to the subject suffering from animmune disorder and having the ABO/Rh blood type of said donor, whereinupon administration of the plasma to the subject, the plasma induces achange in at least one or a combination of biomarkers, thereby treatingthe subject.
 11. The method of claim 10, wherein the immune disorder isimmunosenescence, immune dysfunction, or inflammation.
 12. The method ofclaim 10, wherein the immune disorder is associated with aging.
 13. Themethod of claim 10, wherein the subject suffers from cancer.
 14. Themethod of claim 10, wherein said stem cell mobilization agent is agranulocyte colony stimulating factor (G-CSF).
 15. A method of treatinga subject suffering from an immune disorder comprising: a) preparing anallogeneic cell rich plasma composition by administering to a younghealthy donor a cell mobilization agent in an amount and for a timeperiod sufficient to stimulate a significantly increased number of cellsin the blood of the donor; b) obtaining a sufficient volume of plasma byplasmapheresis from the donor blood by separating cellular material fromthe blood and retaining the cell rich plasma; and c) administering theallogeneic cell rich plasma composition to the subject suffering from animmune disorder and having the ABO/Rh blood type of said donor, whereinupon administration of the plasma to the subject, the plasma induces achange in at least one or a combination of biomarkers, thereby treatingthe subject.
 16. The method of claim 15, wherein the immune disorder isimmunosenescence, immune dysfunction, or inflammation.
 17. The method ofclaim 15, wherein the immune disorder is associated with aging.
 18. Themethod of claim 15, wherein the subject suffers from cancer.
 19. Themethod of claim 15, wherein said cell mobilization agent is agranulocyte colony stimulating factor (G-CSF).
 20. The method of claim15, wherein the allogeneic cell rich plasma comprises stem cells. 21.The method of claim 20, wherein the stem cells comprise lymphoid stemcells.
 22. The method of claim 15, wherein the allogeneic cell richplasma is stem cell rich.
 23. The method of claim 22, wherein the stemcells comprise lymphoid stem cells.